Медицина/6. Экспериментальная и клиническая фармакология

A. S. Gotsulya, prof. O. I. Panasenko, prof. Ye. G. Knysh, O. O. Mikolasyuk

Zaporizhzhya State Medical University, Ukraine

Diuretic activity of 2-[4-(2-methoxyphenyl)-5-R-4Н-1,2,4-triazole-3-ylthio]acetic acid salts

Studying of the impact on renal function of 4-(2-methoxyphenyl)-5-R-1,2,4-triazole-3-thiones and S-derivatives was carried out on outbred white rats, weighing 124-188 g by E. B. Berkhin method.

For investigation of the impact on renal function were used 6 groups of animals, 7 rats in each group. At water diuresis studying rats were maintained on a constant diet with free access to water. Before the water load (5% from body weight) rats were maintained for 2 hours without food and water. Water-soluble compounds that were studied, were injected intraperitoneally in compliance with the rules of asepsis and antisepsis, water-insoluble - orally as an aqueous suspension, stabilized by Tween-80. The compounds were introduced at a dose 1/10 from LD₅₀.

The urine amount was taken into account every hour during 4 hours. The urine amount that allocated the control group of animals (which didn’t receive the studied compounds), taken as 100%. Research and analysis of the obtained experimental facts was performed in comparison with standard diuretics - hypothiazide and furosemide. As experiments showed, the initial thions demonstrate a slight diuretic activity.

Studying of the diuretic activity of salts demonstrated the presence of the expressed diuretic activity at sodium 2-[4-(2-methoxyphenyl)-5-phenyl-4H-1,2,4-triazole-3-ylthio]acetate, ammonium 2-[4-(2-methoxyphenyl)-5-phenyl-4H-1,2,4-triazole-3-ylthio]acetate and potassium 2-[4-(2-methoxyphenyl)-5-methyl-4H-1,2,4-triazole-3-ylthio]acetate.

Diuretic effect of this group of compounds exceeds hypothiazide. Also among this class of compounds were found substances, which by their activity are close to hypothiazide, for example, tretbutylammonium 2-[4-(2-methoxyphenyl)-5-phenyl-4H-1,2,4-triazole-3-ylthio]acetate.

The transition from the sodium 2-[4-(2-methoxyphenyl)-5-methyl-4H-1,2,4-triazole-3-ylthio]acetate to the sodium 2-[4-(2-methoxyphenyl)-5-phenyl-4H-1,2,4-triazole-3-ylthio]acetate is accompanied by a slight increase of the diuretic activity.

Established that the introduction of the phenyl radical instead of methyl at C₅-atom into the tretbutylammonium 2-[4- (2-methoxyphenyl)-5-methyl-4H-1,2,4-triazole-3-ylthio]acetate leads also to the diuresis increasing.

The opposite effect, namely, diuresis decreasing is observed during the methyl radical replacing on the phenyl at C₅-atom at the diethyl 2-[4-(2-methoxy-phenyl)-5-methyl-4H-1,2,4-triazole-3-ylthio]acetate.

In a raw of dіethylammonium 2-[4-(2-methoxyphenyl)-5-methyl-4Н-1,2,4-triazole-3-ylthio]acetate, tretbutylammonium 2-[4-(2-methoxyphenyl)-5-methyl-4Н-1,2,4-triazole-3-ylthio]acetate, sodium 2-[4-(2-methoxyphenyl)-5-methyl-4Н-1,2,4-triazole-3-ylthio]аcetate and potassium 2-[4-(2-methoxyphenyl)-5-methyl-4Н-1,2,4-triazole-3-ylthio]acetate occurs a consecutive increase of the diuretic activity.

The same changes occur in a raw of calcium 2-[4-(2-methoxyphenyl )-5 -phenyl-4H -1,2,4-triazole-3-ylthio]acetate, diethylammonium 2-[4-(2- methoxy- phenyl)-5-phenyl-4H-1,2,4-triazole-3-ylthio]acetate, piperidine 2-[4-(2-methoxy-phenyl)-5-phenyl-4H-1,2,4-triazole-3-ylthio]acetate, tretbutylammonium 2-[4-(2-methoxyphenyl )-5-phenyl-4H-1,2,4- triazole-3-ylthio]acetate, sodium 2-[4-(2-methoxyphenyl)-5-phenyl-4H-1,2,4-triazole-3-ylthio]acetate and ammonium 2-[4-(2-methoxyphenyl)-5-phenyl-4H-1,2,4-triazole-3-ylthio]acetate.

In particular , calcium 2-[4-(2-methoxyphenyl )-5-phenyl-4H -1,2,4-triazole-3- ylthio]acetate demonstrated the lowest results of the diuretic activity.

Among the esters of 2-[4-(2-methoxyphenyl)-5-methyl-4Н-1,2,4-triazole-3-ylthio]аcetate acid and 2-[4-(2-methoxyphenyl)-5-phenyl-4Н-1,2,4-triazol-3-ylthio]acetate acid attract attention the methyl ester of 2-[4-(2-methoxyphenyl)-5-methyl-4Н-1,2,4-triazole-3-ylthio]аcetate acid and the methyl ester of 2-[4-(2- methoxyphenyl)-5-phenyl -4Н-1,2,4-triazol-3-ylthio]acetate acid , diuretic activity of which exceeds analogous indicators of hydrochlorothiazide.

It was also observed that the presence of a direct link between acute toxicity and diuresis: diuresis increasing is accompanied by an increase in acute toxicity. Attracts attention also the butyl ester of 2-[4-(2-methoxyphenyl)-5-phenyl-4Н-1,2,4-triazole-3-ylthio]acetate acid, diuretic activity of which is close to hydrochlorothiazide.

The transition from the methyl ester of 2-[4-(2-methoxyphenyl)-5-methyl-4Н-1,2,4-triazole-3-ylthio]acetate acid to the methyl ester of 2-[4-(2-methoxyphenyl)-5-phenyl-4Н-1,2,4-triazole -3-ylthio]аcetate acid leads to a decrease of diuretic activity.

Substitution in a composition of the ester group of the methyl ester of 2-[4-(2-methoxyphenyl)-5-phenyl-4Н-1,2,4-triazole-3-ylthio]acetate acid residue of methanol alcohol on the n-butyl leads to the dieresis decrease.

Hydrazinolysis of 2-[4-(2-methoxyphenyl)-5-methyl-4Н-1,2,4-triazole-3-ylthio]acetate acid leads to an appearance of a slight antidiuretic action. Instead, obtaining the hydrazide 2-[4-(2-methoxyphenyl)-5-phenyl-4Н-1,2,4-triazol-3-ylthio]acetate acid, slightly increases a dieresis.